The present invention relates generally to methods and apparatus for treating or controlling medical, psychiatric or neurological disorders by application of modulating electrical signals to a selected nerve or nerve bundle of a patient, and more particularly to techniques for treating pain syndromes in patients by selective electrical stimulation of at least one of the trigeminal, glossopharyngeal, vagus and sympathetic nerves.
The most commonly experienced form of pain is attributable to a stimulus on nerve endings, which transmits impulses to the cerebrum. In this nociception or nociceptive pain, a somatic sensation of pain, the organism is informed of impending tissue damage. The pain signals are initially processed by somatic and visceral free nerve endingsxe2x80x94nociceptors. A pathway for nociceptive pain exists within the central nervous system (CNS) through neurons that are the basic excitable cell units of the nerve tissue in the CNS. Each neuron transmits impulse information about the stimulus on the nerve endings along portions of the pathway.
Other types of pain, such as neuropathic pain and psychogenic pain, may develop without actual impending tissue damage. Neuropathic pain involves a disease of the nervous system, usually from an underlying disease process or injury, typically arising after injury to elements of the nervous system involved in nociception. For example, peripheral nerve injury may occur in which the lesions de-afferent the nociceptive pathway, that is, produce a state of loss of afferent input by removal of the incoming signal fiber functions of the pathway.
The nociceptive pathway serves to protect the organism from pain, such as that experienced from a burn. This pathway is inactive unless danger to the organism exists. It begins with activation of peripheral receptors, the signal traveling up the peripheral nerve and into the spinal cord where synapses are made on second order neurons. The latter transmit the pain signal up the spinal cord in the spinothalamic tract ending in the thalamus. The prevailing view is that pain is recognized or perceived in the thalamus. Ventrolateral and ventromedial thalamic nuclei project to the cortex, where the pain is processed respecting localization and other integrative characteristics.
The neuropathic or psychogenic pain pathways are not associated with immediate action to prevent injury. For example, pain experienced following amputation of a limb is neuropathicxe2x80x94no danger of injury exists to the missing limb. Psychogenic pain is a chronic condition of pain without definite organic pathology.
Pain signals originate from peripheral neural receptors, the sensory nerve endings responsive to stimulation, typically from free nerve endings in the skin or the organs. When activated, a graded receptor potential is generated which causes an axon in the nerve fibers to fire action potentials. Action potentials are electrical impulses that self-propagate in a series of polarizations and depolarizations transmitted down the axon. Whether specific pain fibers exist or the sensation of pain comes from recognition of a pattern of impulses, the pain sensations are usually carried by small diameter nerve fibers. Initially, the receptor potential varies in amplitude and may dissipate rapidly with time despite a continuing stimulus, with consequent reduction in the firing frequency in the nerve fiber.
A descending pathway that can inhibit the incoming pain signals is important in the body""s endogenous control of pain. It includes the periaqueductal grey, the dorsal raphe nuclei, locus ceruleus, and nuclei of the medullary reticular formation. Spontaneous activation of the pathway, which may involve activation of the endogenous opiate system, tends to suppress pain transmission.
Other projections from the periphery may also assist to gate pain, for example pain transmission is inhibited with the activation of large diameter A afferents activated by vibration, such as when the individual""s hand is burned and is involuntarily shaken in response. Transcutaneous electrical nerve stimulation (TENS) analgesia also applies this technique, using a non-invasive procedure to submit electrical impulses from an external stimulator through electrodes on the skin to reduce transmission of pain signals to the brain.
Some pain syndromes are associated with an overactive sympathetic nervous system. This occurs following peripheral nerve injury, with resulting pain and sympathetic activity known as causalgia. There is evidence, for example, that norepinephrinexe2x80x94a transmitter of the sympathetic systemxe2x80x94excites nociceptive fibers to produce this abnormal pain. It is possible, however, that aberrant nerve transmission results in activation of sympathetic afferents and to the overactivity.
The sensation of pain is subjective, the clinical reaction differing from patient to patient. The patient""s interpretation of the sensation and its potential sources can lead to apprehension and distress that exacerbates the pain itself. Concentrations of excitatory and inhibitory neurotransmitters in the spinal cord and the brain may vary from individual to individual in response to different stimuli. This may be part of the basis for differences in the tolerance for pain among individuals, and even in the same individual over time. The tolerance for or threshold of pain is, in any case, a dynamic process that depends on the state of the organism, as, for example, instances of minimal pain being experienced for some injuries suffered by soldiers in battle.
The physician""s diagnosis of the site and nature of the underlying pathology of pain depends substantially on historical information provided by the patient. This information includes location of the pain, the extent that it tends to radiate, its intensity, whether it is continual or recurring, the conditions or medications that tend to reduce or increase its severity, in addition to other factors. However, different patients describe pain and its apparent sources in different ways, and some are unable to describe it adequately as to specific site or nature. Prescribing the proper treatment requires an understanding of the underlying organic basis of the pain, and is particularly difficult with patients who experience chronic pain syndromes.
Common complaints include existence of spinal pain, usually in the cervical or lower spine, headache, facial pain, neck pain, and pain in the extremities. Chronic pain that lacks pathological basis is psychogenic, and may be symptomatic of patients suffering from tension, anxiety, depression, hysteria, hypochondria, or simply malingering. But persistent or recurring pain may be neuropathic, attributable to a condition such as arthritis, peripheral nerve pain such as causalgia, or peripheral neuropathy. Hyperpathia and hyperalgesia patients suffer excessive painful reaction to what may constitute normal pain sensations in most individuals.
Drug therapy remains the principal form of treatment for pain, including prescription of analgesics, corticosteroids, antidepressants, topical anesthetics and local anesthetic injections. In acute settings, as after surgery, it is common to prescribe narcotics and anti-inflammatory drugs. For chronic pain, anti-inflammatory drugs are generally the preferred prescription. Other drug therapies in use include tricyclic antidepressants for activating the descending pathways that provide analgesia. Local or systemic administration of anesthetic agents may be used in some cases. Opiates delivered by programmed administration to the cerebrospinal fluid by external drug pumps have been prescribed for patients with intractable pain, especially cancer patients.
TENS analgesia has been most often used for pain following peripheral nerve injury (deafferentation), or for back pain which is chronic and refractory to surgical therapy, or in other cases where surgery is not indicated. Other therapies include dorsal column stimulation and CNS stimulation. The former requires implantation of electrodes in the dorsal column of the spinal cord for activation of fibers to suppress incoming pain signals. CNS stimulation usually involves stimulation of the periaqueductal grey in the midbrain to activate descending inhibitory pathways.
In some, albeit rare situations, ablative procedures are used to control chronic pain by interrupting the afferent pain pathways. The peripheral root may be cut to block incoming fibers. The ventral lateral aspect of the cord that contains spinothalamic fibers may be lesioned. In some cases, sectioning of the cingulate gyrus may aid in controlling pain. In cases where the pain returns, lesions may continue to be made higher up the nervous system axis. It is believed that a pain engram or memory may be formed and distributed in multiple CNS sites.
It is a principal object of the present invention to provide new techniques for treatment of pain through stimulation of certain nerves. In U.S. Pat. No. 5,330,515, assigned to the assignee of the present application, pain therapy is administered by selective stimulation of the patient""s vagus nerve. Pain, especially neuropathic or psychogenic pain, but also nociceptive pain where the patient is suffering from a terminal disease, is treated by application of a programmed, preferably pulse signal to the vagus nerve to excite primarily the small afferent fibers of the nerve. This is intended to activate descending anti-nociceptive pathway to inhibit the chronic or persistent pain being experienced by the patient. In that patent, the preferred but not the only site for the vagus stimulation is in the patient""s neckxe2x80x94the cervical regionxe2x80x94, at a point above the location of the pain felt by the patient, in the sense of a patient standing upright.
The present invention provides improvements in therapy for alleviating chronic or persistent pain, particularly neuropathic and psychogenic pain, by electrical stimulation of any one or more, or all, of the afferent fibers of the trigeminal, vagus and glossopharyngeal nerves, and of the sympathetic nerves, to modulate the electrical activity of the respective nerve or nerves, primarily to activate the descending anti-nociceptive pathway, to inhibit or mask the sensation of pain.
The trigeminal nerve is one (a pair) of the twelve pairs of cranial nerves (or cranial nerves having two branches) of the peripheral nervous system that arise from the brain and branch out from and connect the CNS to other parts of the body. The cranial nerves are also classified as part of the somatic system through which the CNS is connected to the skin and skeletal muscles, concerned with conscious activities of the organism. The trigeminal is one of the mixed nerves of the cranial nerves, with both sensory and motor fibers. It has ophthalmic, maxillary and mandibular divisions, which, as those designations imply, comprise fibers (sensory) that transmit impulses from the region of the eyes, forehead and scalp; from the upper jaw, palate and skin of the face; and from the lower jaw and related areas, respectively; and motor fibers that transmit impulses to muscles of the jaws and mouth.
The vagus nerve is also a mixed pair of the cranial nerves. Its motor fibers transmit impulses to the muscles associated with speech and swallowing, the heart, and smooth muscles of the visceral organs in the thorax and abdomen. Its sensory fibers transmit impulses from the pharynx, larynx, esophagus, and the visceral organs in the thorax and abdomen.
The glossopharyngeal nerve is also a pair among the twelve cranial nerves, and also one of the mixed nerves with both sensory and motor fibers. Its sensory fibers transmit impulses from the carotid arteries, pharynx, tonsils and posterior tongue, while its motor fibers transmit impulses to the salivary glands and the muscles of the pharynx for swallowing.
The sympathetic nerves are a section of the autonomic nervous system. The latter is part of the peripheral nervous system that functions independently and continuously without conscious effort, such as to regulate the individual""s heart rate, blood pressure, body temperature and breathing rate. Sympathetic nerve fibers, like the nerve fibers of the parasympathetic division of the autonomous nervous system, are motor fibers with two neurons, the cell body of one located in the brain or spinal cord and that of the other housed in an autonomic ganglion. The axon of the former is a preganglionic fiber that leaves the CNS and forms a synapse with one or more nerve fibers of an axon of the latter, a postganglionic fiber.
To provide the therapy, a medical interventional device is implanted in the patient at a position in the chest or the abdomen selected to accommodate the patient""s cosmetic desires as well as to be positioned within a region accessible to the designated nerve. The implanted device responds to activation to generate an electrical signal whose parameters are predetermined to deliver the desired therapy to the patient to alleviate or mask the pain. To that end, an electrode at the distal end of an electrical lead is implanted in stimulating and sensing relation onto the designated nerve, which may be the trigeminal, the glossopharyngeal, one of the sympathetics, or the vagus. For example, the electrode may be of a helical design or other suitable conventional design.
The implanted medical interventional device may be activated manually or automatically to deliver the therapeutic signal to the selected nerve via the implanted lead-electrode system, and the device may be programmed to deliver the signal continuously, periodically or intermittently when activated. Preferably, the signal is generated continuously by the device, in the sense of delivery according to its selected parameters, as explained further below. Alternatively, the signal is generated by activation of the device either manually or in response to a detectable symptom of pain or detectable precursor of a pain reaction. To that end, the device may incorporate or otherwise interact with an associated sensor that detects the manifestation of the pain and emits an activating signal to trigger activation of the implanted device. For example, if the patient""s pain is such that it causes spasms or involuntary twitching of a muscle in a particular part of the body affected by the pain, the selected sensor is designed to detect and respond to the spasms or twitching to produce the activating signal for the device to generate its stimulating therapeutic signal.
Alternatively, the therapeutic signal may be generated by the implanted device in response to a command from the patient or attending caregiver upon recognition of the onset of a pain attack, i.e., manually, or prophylactically according to the time of day or to the patient""s circadian rhythm. To allow patient activation, the device is designed to respond to a signal derived from an external source. For example, the patient may perform manual activation whenever pain is perceived, by externally positioning a magnet adjacent the implanted device to operate a reed switch in the device. Other means that may be utilized for patient activation of the implanted device are described in U.S. Pat. No. 5,304,206 to R. G. Baker, Jr. et al. (referred to herein as xe2x80x9cthe ""206 patentxe2x80x9d), which is assigned to the same assignee as the present application. Prophylactic activation is desirable in cases where the patient tends to suffer pain at a certain part of the day, such as arthritic pain in the early evening or early morning. In such a case, the device includes a clock by which a timing signal is emitted for activation at a programmed time or times during the day that the pain is generally experienced.
The therapeutic signal is preferably a pulse waveform having parameters such as pulse amplitude, output current, pulse width, pulse repetition frequency, on/off times, etc., programmed to inhibit pain pathways or receptor potentials. The pulse repetition frequency, pulse width, output current, period, stimulation rate and ON time (duration of a continuous stimulating signal) of the device are programmable. For example, the signal duration may be 30 seconds, provided to the patient with a period of once per hour, using a constant current of 2 ma, with a pulse width of 500 ms and pulse frequency of 20 Hz. But actual values are determined from the nature of the pain and the condition of the patient, as well as by a process referred to herein as spectral optimization which involves step changes in the signal parameters or at least some of them and monitoring the patient""s response or reaction. Spectral optimiztion will be described in greater detail in the detailed description, below.
According to the invention, a predetermined stimulating signal is selectively applied to at least one, and preferably more or all, of the trigeminal, vagus, glossopharyngeal and sympathetic nerves (sometimes referred to herein as the selected cranial nerve(s)) of a patient suffering from pain to treat, control and relieve the symptoms of pain. The stimulating signal to be applied to the selected cranial nerve(s) of the patient is preferably generated by an implanted neurostimulator device such as a neurocybernetic prosthesis (NCP(trademark)) nerve stimulator (generator) available from Cyberonics, Inc., of Houston, Tex., the assignee of the present application. Preferably, the neurostimulator is implanted in the patient, together with appropriate lead(s) and electrode(s) for delivery of the stimulating signal to the selected cranial nerve(s). Alternatively, the signal is applied from an external neurostimulator, to a hospitalized patient. In either case, the signal may be applied continuously, periodically or intermittently, with automatic or manual activation of the generator, depending on the nature, source and symptoms of the pain.
The quality of stimulation of at least one of the designated nerves is important in achieving the desired effect of preventing or controlling the pain. The nerve should be stimulated so as to cause the brain or specific brain processes to alleviate the pain. Several variables of the stimulation need to be controlled to achieve the optimum effect of treating or controlling the pain. In addition, optimization of control of these variables must be determined for each individual patient who is to receive the treatment because of expected variability in the responses of the patients.
A variable for initial consideration is whether only one of the designated nerves should be stimulated, or more than one but less than all should be stimulated, or all of the nerves should be stimulated simultaneously, in the course of treatment of the patient. Although stimulation of all of the nerves will, in general, provide the maximum brain response and pathway activation, and thus increase the likelihood of reaching the target tissues for achieving the desired results of the therapy, it is also true that such stimulation increases the likelihood of reaching non-target tissue(s) and the consequent possibility of undesirable side-reactions. Factors such as the patient""s tolerance to the stimulation, and to the implanting surgery itself, need to be considered in determining the stimulation parameters and the extent of electrode placement.
The selection of the nerve or nerves to be stimulated also requires appropriate consideration of the origin, nature and symptoms of the pain for which the treatment is intended. The trigeminal and vagus nerves generally have a broader range of function and thus are better candidates for application of the stimulating therapeutic signal. For example, the trigeminal nerve, which subserves pain, is the preferred candidate for stimulation to treat pain of central (i.e., brain) origin, whereas the vagus nerve is preferred for treating pain of peripheral origin. The relatively one-dimensional scope of the glossopharyngeal nerve offers the opportunity for more selective brain response. Both the sympathetic and vagus nerves provide an autonomic component to pain ameliorization.